P4HA2 promotes glioma cell proliferation by interacting with Hsp27 to activate the EGFR/ERK signaling pathway.

Prognostic relevance of selected nucleotide variants in canine cutaneous mast cell tumors.

LRRC41 is critical for the progression of multiple cancers, especially hepatocellular carcinoma (HCC), yet its oncogenic mechanism in HCC remains unclear. This study aimed to explore the molecular mechanism by which LRRC41 promotes HCC malignancy and investigate the therapeutic potential of inhibiting its mediated signalling pathway. LRRC41 expression in HCC was analysed via the TCGA, HPA databases and experimental detection. Its biological functions were assessed by in vitro CCK-8, Transwell, colony formation assays and in vivo xenograft models. IP-MS, Co-IP and ubiquitination assays were used to elucidate the molecular mechanism, and the anti-tumour effect of the USP7 inhibitor P6620 was verified in vitro and in vivo. LRRC41 was abnormally overexpressed in HCC and correlated with poor prognosis, promoting HCC cell proliferation, invasion and tumorigenesis. USP7 stabilised LRRC41 via deubiquitination, and LRRC41 activated the NF-κB pathway by targeting HNRNPC in a K63-linked ubiquitination-dependent manner. P6620 inhibited the USP7/LRRC41 axis to suppress HCC malignancy, and its combination with lenvatinib enhanced in vivo anti-tumor efficacy. LRRC41 overexpression drives HCC progression and poor prognosis; the novel USP7/LRRC41/HNRNPC/NF-κB axis is identified in HCC. USP7 inhibitor P6620 blocks this axis and may serve as a potential agent for HCC combination chemotherapy. The regulatory mechanism of the USP7/LRRC41/HNRNPC/NF-κB signalling axis in HCC. Created with Figdraw.

Clinical, pathologic, and molecular profiles of sarcomatoid and rhabdoid differentiated clear cell renal cell carcinoma: A series of 21 tumors.

Phase I trial combining sulfasalazine and gamma knife radiosurgery for recurrent glioblastoma.

Glioblastoma multiforme (GBM) is an aggressive brain tumor characterized by metabolic plasticity and resistance to therapy. Understanding the mechanisms underlying GBM's adaptability to metabolic stress is crucial for developing effective treatments. This study investigates the role of Brain Protein I3 (BRI3) in regulating lipid metabolism and autophagy in GBM, and its potential as a therapeutic target. We performed integrative bioinformatics analysis using TCGA-GBM and CGGA datasets to identify lipophagy-related gene signatures. BRI3's function was examined through in vitro studies using GBM cell lines and patient-derived samples. Lipid metabolism and autophagy were assessed under normal and oxygen-glucose deprivation (OGD) conditions in BRI3-knockdown and control GBM cells. Bioinformatics analysis revealed a lipophagy-related gene signature associated with poor prognosis in GBM. BRI3 emerged as a key upregulated gene in GBM, correlating with altered lipid homeostasis and enhanced autophagy. In vitro studies demonstrated that BRI3 knockdown led to lipid accumulation, impaired autophagy, reduced proliferation, and increased apoptosis in GBM cells. Under OGD conditions mimicking the tumor microenvironment, BRI3-depleted cells showed compromised lipid mobilization, autophagy induction, and cell survival compared to controls. Our findings suggest BRI3 as a critical regulator of lipophagy in GBM, enhancing tumor cell resilience to metabolic stress. This study provides insights into GBM's metabolic adaptability and identifies BRI3 as a potential therapeutic target for modulating tumor cell survival in the challenging glioblastoma microenvironment.

Hyperfractionated reirradiation and PD-1 blockade in recurrent squamous cell head and neck carcinomas with poor prognosis, results from the REPORT-trial.

A targeted approach for ferroptosis induction in neuroblastoma: fsp1 inhibition: abstract SIOPEN AGM 2025

Securinine suppresses pancreatic cancer progression by activating the p38 MAPK pathway to upregulate CHOP and induce endoplasmic reticulum stress.

Plasma exosomal proteomics: Unveiling novel biomarkers for ischemic stroke in the context of diabetes.

Clinical characteristics and mortality risk factors in enterococcal bloodstream infections: a 9-year retrospective cohort study in Japan.

Clinical features and outcomes of fungal bone and joint infections in Western France.

Incidence of cranial and ophthalmic nerve palsy and associated risk factors in tuberculous meningitis: A systematic review and meta-regression analysis.

Lung adenocarcinoma (LUAD) has limited therapeutic targets and poor survival. Noncanonical open reading frames (ORFs) in long noncoding RNAs (lncRNAs) may encode functional microproteins, but their roles in LUAD remain unclear. This study aims to characterise the LINC00973-encoded microprotein L3EMP and to investigate its tumour-promoting mechanisms and therapeutic potential. L3EMP was identified through ribosome profiling and RNA sequencing, with its expression confirmed by mass spectrometry (MS) and Western blotting. Its functional relevance was further validated using CRISPR/Cas9-mediated gene manipulation. Functional experiments were performed in LUAD cells and chimeric antigen receptor T (CAR-T) cell models to elucidate the underlying molecular mechanisms. The interaction between USP22 and SIRT1 was investigated via ubiquitination assays and signalling pathway profiling. Finally, immunotherapeutic potential was evaluated using synthetic L3EMP peptides and B7-H3-targeted CAR-T cells. (1) L3EMP, a microprotein encoded by LINC00973, is overexpressed in LUAD and its expression level is correlated with poor prognosis. (2) L3EMP stabilises SIRT1 by promoting USP22-mediated deubiquitination. This forms a positive feedback loop involving YY1 that activates AKT/ERK signalling, thereby promoting proliferation and invasion. (3) L3EMP knockout suppresses tumour growth in PDX models. (4) Synthetic L3EMP peptide enhances antitumor immunity as a neoantigen. (5) L3EMP deletion synergises with B7-H3 CAR-T therapy via IFN-γ pathway activation. L3EMP contributes to LUAD progression through the USP22/SIRT1 signalling axis and represents both a therapeutic target and an immunogenic neoantigen. Targeting L3EMP or its pathway inhibits tumour growth, while the synthetic L3EMP peptide can potentiate immunotherapy. The combination of L3EMP depletion and B7-H3 CAR-T therapy enhances antitumor efficacy, suggesting a promising combinatorial strategy for LUAD treatment.

Outcomes and prognostic factors of hematopoietic stem cell transplantation in adult patients with acute myeloid leukemia and central nervous system involvement.

Scutellarein inhibits the malignancy of gliomas by modulating the PI3K/AKT signaling pathway.

Leptomeningeal metastasis (LM) is an aggressive complication characterized by the dissemination of malignant cells to the leptomeninges, typically resulting in rapid neurological deterioration and poor prognosis. Clinical diagnosis and management are impeded by non-specific symptoms and the limited sensitivity of conventional cerebrospinal fluid (CSF) cytology. Consequently, CSF biomarkers have emerged as critical tools for diagnosis, treatment monitoring and prognostic evaluation. The present review summarizes recent advancements in CSF biomarkers, categorizing them into proteins, nucleic acids and metabolites. These biomarkers enhance diagnostic accuracy, facilitate longitudinal disease tracking and assess therapeutic efficacy. Despite notable progress, challenges persist regarding biomarker sensitivity, specificity and standardization. Furthermore, the potential of multi-omics technologies and single-cell analysis is discussed as a pathway for discovering novel biomarkers to enable the precise stratification and personalized management of LM.

Ferroptosis mechanisms in early brain injury after subarachnoid hemorrhage.

Neuroendocrine prostate cancer (NEPC) is characterized by its aggressive biological behavior and poor prognosis, distinguishing it from prostate adenocarcinoma. Although several studies have investigated tumor markers associated with neuroendocrine differentiation and treatment outcomes, there is a lack of research focusing specifically on treatment-naive prostate cancer. This study aims to evaluate neuroendocrine differentiation and the relationship between neuroendocrine markers (neuron-specific enolase (NSE) and pro-gastrin releasing peptide (pro-GRP)) and the aggressiveness of prostate cancer at the time of diagnosis. A total of 310 prostate cancer cases diagnosed through biopsy between October 2019 and January 2024 were analyzed. This study focused on neuroendocrine tumor markers, NSE and pro-GRP, to evaluate the incidence of neuroendocrine differentiation. Furthermore, the relationship between these markers and tumor aggressiveness was examined, as determined by clinical T-stage (cT), lymph node (LN) metastasis, and distant metastasis at the time of diagnosis. The incidence of positive neuroendocrine markers, defined as the presence of at least one marker exceeding the normal threshold, was 25.8%. A significant correlation was identified only between prostate-specific antigen (PSA) and pro-GRP (p < 0.001). No significant relationships were observed between PSA and NSE, or between NSE and pro-GRP (p = 0.434 and p = 0.918, respectively). In multivariate analyses for cT ≥ 3, PSA, Ki-67, and pro-GRP were significant factors (p < 0.01, p < 0.001, and p = 0.0153, respectively). For positive LN metastasis, PSA and Ki-67 were significant (p = 0.0178 and p < 0.0001, respectively). For positive distant metastasis, PSA, Ki-67, and pro-GRP were significant (p < 0.001, p = 0.0130, and p = 0.0128, respectively). Neuroendocrine tumor markers, specifically NSE and pro-GRP, were positive in approximately 25% of treatment-naive prostate cancer cases. While NSE did not correlate with tumor aggressiveness, pro-GRP was associated with it and emerged as an independent factor related to tumor aggressiveness. These findings suggest that, despite both markers being linked to the same tumor type, they may exhibit distinct biological characteristics, warranting further investigation.

MSR1+ tumor-associated macrophages (TAMs) have been implicated in various malignancies; however, their functional role in Hepatocellular carcinoma (HCC) remains poorly defined. This research seeks to clarify the roles of MSR1+ TAMs in HCC and their influence on the tumor immune microenvironment. Clinical and experimental data indicate that high levels of MSR1+ TAMs correlate with poor prognosis in HCC patients. Transcriptomic analyses and in vitro as well as in vivo functional assays revealed that the immunosuppressive activity of MSR1+ TAMs is closely linked to their secretory profile. MSR1 enhances IL-6 secretion by activating the NF-κB signaling pathway, subsequently facilitating the recruitment of myeloid-derived suppressor cells (MDSCs). This cascade diminishes CD8+ T cell infiltration and effector function, promoting an immunosuppressive tumor microenvironment. In preclinical models, the simultaneous inhibition of MSR1 and PD-L1 markedly reduced tumor growth more effectively than either treatment alone. Our findings demonstrate that MSR1+ TAMs contribute to hepatocellular carcinogenesis through the NF-κB/IL-6 signaling axis by promoting MDSCs accumulation and impairing CD8+ T cell responses. Effectively targeting MSR1+ TAMs can overcome resistance to anti-PD-L1 therapy, offering a promising new immunotherapeutic approach for HCC.